• International Journal of Industrial Entomology and Biomaterials
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• 제43권2호
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• pp.45-51
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• 2021

High blood cholesterol levels and oxidized cholesterol are risk factors for cardiovascular disease, which displays high annual incidence. Although studies on sericulture products, including pupae, silk protein, and blood lymph, as hypocholesterolemic substances have been reported, insufficient research in this field has been focused on silkworm larvae. Six larval extracts (Low temperature distilled water, LW; hot temperature distilled water, HW; and 30-100% ethanol, E30-E100) were prepared, and their effects on cholesterol metabolism were examined. LW most potently reduced the risk of cholesterol-related disorders. Polyphenols were highly represented in LW, corresponding with its increased antioxidant potency. The cholesterol biosynthesis enzyme, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) was strongly inhibited by LW. Hepatocytes over-expressed LDL receptor (LDLR) after LW stimulation, promoting cholesterol elimination from plasma. LW also increased ATP binding cassette transporter 1 (ABCA1) gene expression, upregulating HDL biogenesis. In conclusion, LW exhibited strong antioxidant activity, suppressed cholesterol biosynthesis, improved LDL uptake from plasma, and upregulated HDL biosynthesis. In aggregate, these activities could reduce blood cholesterol levels and prevent cardiovascular disease.

• BMB Reports
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• 제38권2호
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• pp.225-231
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• 2005

Acid-labile subunit (ALS) is a component of the 150-kDa insulin-like growth factor-binding protein-3 (IGFBP-3) complex, which, by sequestering the majority of IGFs-I and -II and thereby prolonging the half-life of them in plasma, serves as a circulating reservoir of IGFs in mammalian species. A pGEX-2T plasmid and a baculovirus expression constructs harboring a coding sequence for glutathione-S transferase (GST)-porcine ALS (pALS) fusion protein were expressed in BL21(DE3) E. coli and Sf9 insect cells, respectively. The expressed protein was purified by glutathione or Ni-NTN affinity chromatography, followed by cleavage of the fusion protein using Factor Xa. In addition, pALS and hIGFBP-3 were also produced in small amounts in the Xenopus oocyte expression system which does not require any purification procedure. A 65-kDa pALS polypeptide was obtained following the prokaryotic expression and the enzymatic digestion, but biochemical characterization of this polypeptide was precluded because of an extremely low expression efficiency. The baculovirus-as well as Xenopus-expressed pALS exhibited the expected molecular mass of 85 kDa which was reduced into 75 and 65 kDa following deglycosylation of Asn-linked carbohydrates by Endo-F glycosidase, indicating that the expressed pALS was properly glycosylated. Moreover, irrespective of the source of pALS, the recombinant pALS and hIGFBP-3 formed a 130-kDa binary complex which could be immunoprecipitated by anti-hIGFBP-3 antibodies. Collectively, results indicate that an authentic pALS protein can be produced by the current expression systems.

• Preventive Nutrition and Food Science
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• 제1권1호
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• pp.134-142
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• 1996

Diabetes carries an increased risk of atherosclerotic disease that is not fully explained by known car-diovascular risk factors. There is accumulating evidence that advanced glycation of structural proteins, and oxidation and glycation of circulating lipoproteins, are implicated in the pathogenesis of diabetic ather-osclerosis. Reactions involving glycation and oxidation of proteins and lipids are believed to contribute to atherogenesis. Glycation, the nonenzymatic binding of glucose to protein molecules, can increase the ather-ogenic potential of certain plasma constituents, including low density lipoptotein(LDL). Glycation of LDL is significant increased in diabetic patients compared with normal subjects, even in the presence of good glycemic control. Metabolic abnormalities associated with glycation of LDL include diminished recognition of LDL by the classic LDL receptor; increased covalent binding of LDL in vessel walls ; enhanced uptake of LDL by the macrophages, thus stimulating foam cell formation ; increased platelet aggregation; formation of LDL-immune complexes ; and generation of oxygen free radicals, resulting on oxidative damage to both the lipid and protein components of LDL and to any nearby macromolecules. Oxidized lipoproteins are characterzied by cytotoxicity, potent stimulation of foam cell formation by macrophages, and procoagulant effects. Combined glycation and oxidation, "glycoxidation" occurs when oxidative reactions affect the initial products of glycation, and results in irreversible structural alterations of proteins. Glycoxidation is of greatest significance in long lived proteins such as collagen. In these proteins, glycoxidation products, believed to be atherogenic, accumulate with advancing age : in diabetes, their rate of accumulate is accelerated. Inhibition of glycation, oxidation and glycoxidation may form the basis of future antiaterogenic strategies in both diabetic and nondiabetic individuals.dividuals.

• 약학회지
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• 제28권4호
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• pp.207-215
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• 1984

Effects of Ssang Wha Tang (SWT), a blended Chinease traditional medicine, on the pharmacokinetics of sulfobromophthalein (BSP) in the rats of hepatic failure induced by carbon tetrachloride were examined. The disposition of plasma BSP in carbon tetrachloride-treated rats (Group I) and in carbon tetrachloride+SWT-treated rats (Group II) followed a three-compartment model, while those in control group followed two-compartment model. GOT, GPT level and some pharmacokinetic paramiters like plasma clearance but except distribution volume (Vdss) recovered in Group II compared to Group I. Therefore, SWT seemed to have an apparent restoring effect of hepatic function damaged by carbon tetrachloride treatment. From the fact that Vdss of BSP in Group II was considered as an one of the probable mechanisms. More intensive increase in BSP-free fraction ($f_p$) in Group II than that in Group I might also explain the increases of BSP clearance and Vdss in Group II compared to Group I. Assuming no changes in hepatic plasma flow(Q) in each group, hepatic intrinsic clearance($CL^h_{int}$) decreased in Group I did not recovered not at all in Group II. Therefore SWT seemed not to have any restoring effect of true hepaticfunction to biotransform and excrete BSP, and the apparent restoring effect of SWT might be due only to the replacement of BSP-plasma protein binding. Whether $f_p$ is actually higer in Group II than in Group I, and Q is constant in each group are being examined in our laboratory. The changes of Q, which might lead to another conculusions, also should be taken into consideration to clarify the apparent hepatorestoring effect of SWT.

• 생명과학회지
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• 제20권10호
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• pp.1451-1457
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• 2010

Serotonin (5-hydroxytryptamine (5-HT))는 신경계의 세포-세포 간의 신호전달의 주요한 신경전달물질이다. 세포막에 존재하는 serotonin transporter (SERT)는 연접간격에 존재하는 5-HT를 세포 내로 재흡수 하여 세포외부의 5-HT 농도를 조절하지만 그 기전은 아직 밝혀지지 않았다. 본 연구에서는 yeast two-hybrid system을 사용하여 SERT의 C-말단이 protein kinase C-$\varepsilon$ (PKC-$\varepsilon$)과 특이적으로 결합함을 알았다. PKC-$\varepsilon$는 PKC의 isotype으로 calcium 비의존적이며 phorbol ester/diacylglycerol 민감성 serine/threonine kinase이다. $Na^+/Cl^-$ 의존성 SLC6 gene family의 다른 수송체는 PKC-$\varepsilon$과 결합하지 않았다. Deletion mutant들을 사용하여 SERT는 PKC-$\varepsilon$의 C-말단부위와 결합함을 알았으며, 또한 이 단백질간의 결합을 GST pull-down assay로 확인하였다. PKC-$\varepsilon$는 in vitro에서 SERT의 N-말단의 펩티드를 인산화시켰다. 이러한 결과들은 PKC-$\varepsilon$에 의한 SERT의 인산화가 세포막에 존재하는 SERT의 활성을 조절하는 역할을 할 가능성을 시사한다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.173-173
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• 1996

포도당 수송을 증가시키는 것으로 밝혀진 brazilin의 작용이 지방세포의 단백질과 결합하여 나타나는지 알아보기 위한 실험으로 brazilin의 단백결합 성질을 살펴보았다. Brazilin의 단백결합 실험에는 [$^3$H]-brazilin을 사용하여 결합된 양을 방사선 동위원소량으로 확인하였다. 먼저 일반적인 단백결합을 알아보기 위하여 산침전을 이용한 brazilin의 BSA에 대한 결합을 살펴보았다. 그 결과 brazilin은 시간의 경과에 따라 BSA에 결합하는 양이 증가하여 2시간에 최고치에 달했으며 그 양은 약 80% 정도였다. 세포내 단백과의 결합은 BSA에 대한 결합과는 달리 1시간만에 최고치에 달하였다. 세포내 분획에 분포하는 brazilin의 양을 알기 위하여 brazilin처리 후 세포내 분획을 원심분리로 얻어 brazilin의 양을 확인하였다. 그 결과 brazilin은 cytosol에 대부분 존재하며 microsomal membrane과 nuclear에 많은 양이 존재하는 것으로 확인되었다. SDS-PAGE를 이용하여 brazilin과 결합한 각 분획의 단백질을 살펴본 결과 brazilin은 cytosol의 30, 65KD, microsomal membrane의 45, 130KD, nucear의 26, 35KD, plasma membrane의 46, 228KD protein과 반응하는 것으로 확인되었다.

• Pediatric Infection and Vaccine
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• 제3권1호
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• pp.66-74
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• 1996

There continues to be increasing the number of patients being treated for renal failure day by day due to lot of causes. It is prerequsite for the physician to have a proper understanding of drug use in patients with renal failure since kidney is the major route of elimination for many kinds of drugs and their metabolites. In order to provide practical guidelines for prescribing antibiotics, the literature has been reviewed, and summarized. The tables presented here are made by Dr. William M Bennett et al. and listed the specific pharmacokinetic information such as drug half life, serum levels, and drug removal during dialysis, plasma protein binding, volume of distribution.

• 약학회지
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• 제35권1호
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• pp.38-44
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• 1991

It has been reported that the pharmacokinetic behaviors of drugs which are mostly metabolized in the liver are significantly different in patients with renal failure. Theophylline(TP) is mainly metabolized in the liver (approximately 90%) and renal clearance of the drug is negligible (less than 10%). Therefore, we have investigated the changes in pharmacokinetics of theophylline in normal, G-ARF and U-ARF rats after an intravenous administration. The total body clearance of TP decreased approximately 40% in U-ARF rats. The reduced CL$_{T}$, value in U-ARF rats could be due to reduced hepatic intrinsic clearance by up to 40% since it has been published that plasma protein binding of TP and liver blood flow does not change in U-ARF rats.

• 생물정신의학
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• 제7권1호
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• pp.21-33
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• 2000

As the clinical practice of using more than one drug at a time increase, the clinician is faced with ever-increasing number of potential drug interactions. Although many interactions have little clinical significances, some may interfere with treatment or even be life-threatening. This review provides a better understanding of drug-drug interactions often encountered in pharmacotherapy of depression. Drug interactions can be grouped into two principal subdivisions : pharmacokinetic and pharmacodynamic. These subgroups serve to focus attention on possible sites of interaction as a drug moves from the site of administration and absorption to its site of action. Pharmacokinetic processes are those that include transport to and from the receptor site and consist of absorption, distribution on body tissue, plasma protein binding, metabolism, and excretion. Pharmacodynamic interactions occur at biologically active sites. In this review, emphasis is placed on antidepressant medications, how they are metabolized by the P450 system, and how they alter the metabolism of other drugs. When prescribing antidepressant medications, the clinician must consider the drug-drug interactions that are potentially problematic.

• Journal of Ginseng Research
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• 제34권4호
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• pp.369-375
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• 2010

This study evaluated the protective effects of ginseng leaf extract (GLE) against high fat-diet-induced hyperglycemia and hyperlipidemia, and explored the potential mechanism underlying these effects in C57BL/6J mice. The mice were randomly divided into four groups: normal control, high fat diet control (HFD), GLE-treated at 250 mg/kg, and GLE-treated at 500 mg/kg. To induce hyperglycemic and hyperlipidemic states, mice were fed a high fat diet for 6 weeks and then administered GLE once daily for 8 weeks. At the end of the treatment, we examined the effects of GLE on plasma glucose, lipid levels, and the expression of genes related to lipogenesis, lipolysis, and gluconeogenesis. Both GLE groups lowered levels of plasma glucose, insulin, triglycerides, total cholesterol, and non-esterified fatty acids when compared to those in HFD group. Histological analysis revealed significantly fewer lipid droplets in the livers of GLE-treated mice compared with HFD mice. To elucidate the mechanism, Western blots and RT-PCR were performed using liver tissue. Compared with HFD mice, GLE-treated mice showed higher levels of phosphorylation of AMP-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase, but no differences in the expression of lipogenic genes such as sterol regulatory element-binding protein 1a, fatty acid synthase, sterol-CoA desaturase 1 and glycerol-3-phosphate acyltransferase. However, the expression levels of lipolysis and fatty acid uptake genes such as peroxisome proliferator-activated receptor-$\alpha$ and CD36 were increased. In addition, phosphoenolpyruvate carboxykinase gene expression was decreased. These results suggest that GLE ameliorates hyperglycemia and hyperlipidemia by inhibiting gluconeogenesis and stimulating lipolysis, respectively, via AMPK activation.